A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies
- Conditions
- Interventions
- Registration Number
- NCT06634589
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study is to measure the safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics with BGB-16673 in combination with other agents in participants with relapsed or refractory (R/R) B-cell malignancies. This study is structured as a master protocol with separate substudies. This study will initially include two substudi...
- Detailed Description
This new study will check how safe and helpful a potential anticancer drug called BGB-16673 is in participants with R/R B-cell malignancies when it is given in combination with other medicines - sonrotoclax in substudy 1, and with zanubrutinib in substudy 2.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
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Must sign the informed consent form (ICF) and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF
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Confirmed diagnosis of a R/R B-cell malignancy
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Protocol-defined measurable disease
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Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
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Adequate organ function
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Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for 30 days after the last dose of BGB-16673 or zanubrutinib, or 90 days after the last dose of sonrotoclax. A negative urine or serum pregnancy test result must be provided 10-14 days before the first dose of study treatment
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Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for 30 days after the last dose of BGB-16673 or zanubrutinib, or 90 days after the last dose of sonrotoclax
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Substudy 2 Inclusion Criteria:
- Bruton tyrosine kinase (BTK) inhibitor-naive, or
- Previously received treatment with a covalent BTK inhibitor and discontinued for reasons other than clinical progression
Key
-
Treatment-naive B-cell malignancies
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Unable to comply with the requirements of the protocol
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Active leptomeningeal disease or uncontrolled, untreated brain metastasis
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Any malignancy ≤ 2 years before first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively
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Autologous stem cell transplant ≤ 3 months prior to screening or chimeric antigen T-cell therapy ≤ 3 months prior to screening
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Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
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Participants who have a history of severe allergic reactions or hypersensitivity to the active ingredient and excipients of BGB-16673, sonrotoclax, or zanubrutinib
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Substudy 1 Exclusion Criterion:
- Prior treatment with a B-cell lymphoma-2 (Bcl-2) inhibitor
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Substudy 2 Exclusion Criterion:
- Participants who discontinued prior zanubrutinib treatment due to intolerance
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 1 Part 1b: Safety Expansion BGB-16673 Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell histologies. Substudy 1 Part 1b: Safety Expansion sonrotoclax Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell histologies. Substudy 2 Part 1a: Dose Escalation BGB-16673 Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated. Substudy 2 Part 1a: Dose Escalation Zanubrutinib Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated. Substudy 2 Part 1b: Safety Expansion BGB-16673 Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell histologies. Substudy 1 Part 1a: Dose Escalation BGB-16673 Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated. Substudy 1 Part 1a: Dose Escalation sonrotoclax Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated. Substudy 2 Part 1b: Safety Expansion Zanubrutinib Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell histologies.
- Primary Outcome Measures
Name Time Method Substudy 1 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 1 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 2 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 2 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
- Secondary Outcome Measures
Name Time Method Substudy 1 Part 1a and 1b: Overall Response Rate (ORR) for BGB-16673 and sonrotoclax Up to approximately 3 years ORR is defined as the percentage of participants with complete response (CR) or partial response (PR)
Substudy 1 Part 1a and 1b: Duration of Response (DOR) for BGB-16673 and sonrotoclax Up to approximately 3 years DOR is defined as the time from the first objective response to disease progression documented after treatment initiation or death, whichever occurs first.
Substudy 1 Part 1a and 1b: Time to Response (TTR) for BGB-16673 and sonrotoclax Up to approximately 3 years TTR is defined as the time from treatment initiation to first response
Substudy 1 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1a: Terminal half-life (t1/2) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1a: Trough concentration (Ctrough) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1b: Number of patients with complete response or complete response with incomplete count recovery (CR/CRi) who achieve undetectable minimal residual disease (uMRD) Up to approximately 3 years Substudy 2 Part 1a and 1b: ORR for BGB-16673 and zanubrutinib Up to approximately 3 years ORR is defined as the percentage of participants with complete response (CR) or partial response (PR)
Substudy 2 Part 1a and 1b: DOR for BGB-16673 and zanubrutinib Up to approximately 3 years DOR is defined as the time from the first objective response to disease progression documented after treatment initiation or death, whichever occurs first.
Substudy 2 Part 1a and 1b: TTR for BGB-16673 and zanubrutinib Up to approximately 3 years TTR is defined as the time from treatment initiation to the first response.
Substudy 2 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 2 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 2 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 2 Part 1a: Terminal half-life (t1/2) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 2 Part 1a: Trough concentration (Ctrough) of BGB-16673 and zanubrutinib From Week 1 to Week 17
Trial Locations
- Locations (43)
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Summit Medical Group
🇺🇸Florham Park, New Jersey, United States
Weill Cornell Medical College Newyork Presbyterian Hospital
🇺🇸New York, New York, United States
Icahn School of Medicine At Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center Mskcc
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Mater Cancer Care Centre
🇦🇺South Brisbane, Queensland, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital, Zhejiang University School of Medicinechengzhan
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
🇩🇪Dresden, Germany
Universitatsklinikum Jena Klinik Fur Innere Medizin Ii
🇩🇪Jena, Germany
Universitatsklinikum Schleswig Holstein, Campus Kiel
🇩🇪Kiel, Germany
Medizinische Universitaetsklinik
🇩🇪Tuebingen, Germany
Universitaetsklinikum Ulm, Innere Medizin Iii
🇩🇪Ulm, Germany
Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
🇮🇹Bologna, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Istituto Nazionale Tumori Fondazione G Pascale
🇮🇹Napoli, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Centro Ricerche Cliniche Di Verona
🇮🇹Verona, Italy
Auckland City Hospital
🇳🇿Auckland, New Zealand
North Shore Hospital
🇳🇿Takapuna, New Zealand
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Samodzielny Publiczny Szpital Kliniczny Nr W Lublinie
🇵🇱Lublin, Poland
Szpital Kliniczny Mswia Z Warmisko Mazurskim Centrum Onkologii
🇵🇱Olsztyn, Poland
Szpital Wojewodzki W Opolu Sp Z Oo Oddzia Hematologii I Onkologii Hematologicznej
🇵🇱Opole, Poland
Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Hematology Unit
🇵🇱Warsaw, Poland